1. Field of the Invention
The present invention relates to a detection device for detecting a magnetic particle in a sample solution, a detecting method and a detection kit.
2. Related Background Art
A number of techniques such as radioimmunoanalysis and enzyme antibody technique have been proposed and implemented as immunoanalysis until now. For example, in radio-immunoassay (RIA) or immunoradiometric assay (IRMA), a competitive antigen or antibody is labeled with a radionuclide, and the antigen is quantitatively measured based on measurement results of a specific activity. An advantage of this method is its high sensitivity, but a special facility or apparatus is necessary in view of the safety of radionuclides. The enzyme antibody technique using an enzyme for labeling an antibody can be handled more easily than radioimmunoanalysis and provides a practical sensitivity. However, higher sensitivity and more ease of handling are demanded.
Under these circumstances, methods for readily detecting, by using giant magnetoresistive effect (GMR) elements, a small amount of magnetic particles used as labeling substances have been proposed in recent years (for example, David R. Baselt, et al., “Biosensors & Bioelectronics 13,731” (1998)(document 1), D. L. Graham, et al., “Biosensors & Bioelectronics 18,483” (2003)(document 2)).
In document 1, GMR films of 80 μm×5 μm and 20 μm×5 μm are used and a plurality of magnetic particles with a diameter of 2.8 μm are detected. FIG. 4 shows that a stray magnetic field is applied from a magnetic particle to a GMR film. A magnetic film used for the GMR film is an in-plane magnetized film, and a magnetic field 180 is applied to the magnetic particle perpendicularly to a surface of the magnetic film. Therefore, as shown in FIG. 4, a stray magnetic field 182 generated from a magnetic particle 174 is applied to the magnetic film of a GMR film 300 almost in the in-plane direction of the film. The magnetic particle 174 has been magnetized by the application of the magnetic field. The magnetization of the magnetic film is aligned with the direction of the magnetic field. Reference numeral 181 denotes the magnetization direction of the magnetic particle.
The electrical resistance of the GMR element depends upon the relative magnetization directions of two magnetic films. Parallel magnetization has a relatively low electrical resistance. Antiparallel magnetization has a relatively high electrical resistance. In order to obtain parallel and antiparallel magnetization, the magnetization direction of one of the two magnetic films of the GMR element is fixed, and the other of the magnetic films is made of a magnetic material having a coercive force allowing a stray magnetic field from a magnetic particle to reverse magnetization. In the absence of a magnetic particle on the GMR element, even when an external magnetic field is applied, a magnetic field is not applied to the magnetic film in the in-plane direction of the film, and so magnetization is not reversed. Further, a detection circuit is configured as follows: a bridge circuit is constituted of two fixed resistors, a GMR element where a magnetic particle is not fixed, and a GMR element where a magnetic particle can be fixed. A potential difference induced by the bridge circuit is detected by a locking amplifier.
In document 2, GMR elements of 2 μm×6 μm are used and a magnetic particle having a diameter of 2 μm is detected. As in document 1, the GMR element where a magnetic particle can be fixed and the GMR element where a magnetic particle cannot be fixed are formed side by side, and the output signals of the two GMR elements are compared with each other, so that a magnetic particle is detected. A magnetic film is an in-plane magnetized film, and a magnetic field is applied to the magnetic particle in the longitudinal direction of the magnetic film in the plane of the film.
As described above, in the methods of detecting a magnetic particle by using the GMR elements, a magnetic particle is magnetized in a desired direction and the magnetization direction of a magnetoresistive effect film is changed by a stray magnetic field generated from the magnetic particle, thereby achieving ease of handling and detection in a relatively short time.
As described above, the electrical resistance of the magnetoresistive effect film is changed by the magnetization of the two magnetic films. In the magnetic film where magnetization can be reversed, when a region where magnetization is reversed is only a part of the magnetic film, the resulting magnetoresistance effect becomes smaller than that of a magnetic film where magnetization is entirely reversed. For example, when a magnetic particle has a small diameter and a magnetoresistive effect film has quite a small region of reversed magnetization, the resulting change in electrical resistance is small, and thus detection cannot be made.
Particularly in the case of a stray magnetic field of superparamagnetism, when the application of an external magnetic field to the magnetic particle is stopped, a stray magnetic field is not generated from the magnetic particle and a small magnetic domain easily disappears, which has been formed locally on the magnetic film of the magnetoresistive effect film. Thus, it becomes difficult to store information on the detected magnetic particle.